{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:06:04Z","timestamp":1785409564306,"version":"3.56.0"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82060160"],"award-info":[{"award-number":["82060160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: In the diabetic heart, hyperglycemia can augment the covalent modification of Ca2+-calmodulin-dependent protein kinase II (CaMKII) by O-linked N-acetylglucosamine (O-GlcNAc). Concurrently, mitophagy serves as a crucial link in diabetic myocardial injury. The association between these two processes in diabetic cardiomyopathy remains to be elucidated. Methods: A rat model of type 1 diabetes was constructed via a single intraperitoneal injection of streptozotocin (STZ; 50\u00a0mg\/kg). The regulatory mechanism by which O-GlcNAc-modified CaMKII affects mitophagy was determined via bioinformatics analysis and coimmunoprecipitation. Results: At 12\u00a0weeks after STZ induction, the rats presented with decreased cardiac function and myocardial injury, accompanied by increased O-GlcNAc modification of CaMKII and significant accumulation of the autophagy markers LC3II\/I and P62. Electron microscopy showed an increase in damaged mitochondria and autophagosomes, suggesting that mitophagic flux was inhibited. Bioinformatics analysis identified heat shock protein \u03b2-8 (HSPB8) as a crucial autophagy-related protein downstream of CaMKII. The findings confirmed that the adenovirus overexpressing HSPB8 was capable of ameliorating the cardiomyocyte injury induced by high glucose both in vivo and in vitro, effectively facilitating mitophagic flux. An elevation in O-GlcNAc enhances the interaction between CaMKII and HSPB8, exacerbating the inhibitory effect on autophagosome degradation. In contrast, O-GlcNAc inhibitors can effectively mitigate this inhibitory condition. Conclusions: In diabetic rats, an increase in O-GlcNAc can facilitate the binding of its substrate CaMKII to HSPB8, thereby suppressing mitophagic flux and exacerbating myocardial injury.<\/jats:p>","DOI":"10.1042\/cs20260408","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:29:44Z","timestamp":1784730584000},"page":"1779-1797","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["O-GlcNAc modification of CaMKII-mediated mitophagic flux regulation via HSPB8 in diabetic cardiomyopathy"],"prefix":"10.1042","volume":"140","author":[{"given":"Yanjuan","family":"Jiang","sequence":"first","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"},{"name":"2The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaibo","family":"Hu","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"},{"name":"3Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Luo","sequence":"additional","affiliation":[{"name":"4Huan Kui College of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Duan","sequence":"additional","affiliation":[{"name":"2The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Qi","sequence":"additional","affiliation":[{"name":"2The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China"},{"name":"5Queen Mary School, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zheng","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"6Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zou","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Cai","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Niu","sequence":"additional","affiliation":[{"name":"4Huan Kui College of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"},{"name":"2The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China"},{"name":"7Center for Clinical Precision Medicine, Jiujiang University, Jiujiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-0279","authenticated-orcid":false,"given":"Xiaoyang","family":"Lai","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"2026073006321047500_B1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/0002-9149(72)90595-4","article-title":"New type of cardiomyopathy associated with diabetic glomerulosclerosis","volume":"30","author":"Rubler","year":"1972","journal-title":"Am. 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